Lewis Acid-Promoted [2 + 1] Cycloaddition Reactions of a 1-Seleno-2

Shoko Yamazaki, Yuichiro Yanase, Etsuko Tanigawa, and Shinichi Yamabe , Hatsue Tamura. The Journal of Organic Chemistry 1999 64 (26), 9521-9528...
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J. Org. Chem. 1998, 63, 5919-5928

5919

Lewis Acid-Promoted [2 + 1] Cycloaddition Reactions of a 1-Seleno-2-silylethene to 2-Phosphonoacrylates: Stereoselective Synthesis of a Novel Functionalized r-Aminocyclopropanephosphonic Acid Shoko Yamazaki,* Takashi Takada, Tomomi Imanishi, Yumiko Moriguchi, and Shinichi Yamabe Department of Chemistry, Nara University of Education, Takabatake-cho, Nara 630-8258, Japan Received March 24, 1998

Stereoselective SnCl4-promoted [2 + 1] cycloaddition reactions of 1-seleno-2-silylethene 1 with 2-phosphonoacrylates 2 lead to highly functionalized cyclopropanephosphonate esters 3 in high yields. The cyclopropane products 3 are potentially versatile starting materials for biologically important compounds. Stereoselective synthesis of a novel functionalized R-aminophosphonic acid derivative, an analogue of (Z)-2,3-methanohomoserine 13, from the cycloadduct 3b was achieved. Stereoselectivity in the [2 + 1] cycloaddition was explained by consideration of the structure of the 2-SnCl4 complex. Introduction Cyclopropane derivatives play an important role in biological activity1 and synthetic chemistry.2 Furthermore, they also function as conformationally constrained amino acid analogues3 and mechanistic probes to determine reaction pathways.4 In this regard, development of novel methods of cyclopropanation presents a challenging area of research in current organic chemistry.5 We have recently reported a novel [2 + 1] cycloaddition strategy involving reaction of (E)-1-phenylseleno-2-silylethenes with electrophilic olefins, to afford cyclopropane products with high stereoselectivity in the presence of Lewis acids.6 This new approach to cyclopropane con(1) For reviews, see: (a) Salau¨n, J.; Baird, M. S. Curr. Med. Chem. 1995, 2, 511. (b) Liu, H. W.; Walsh, C. T. Biochemistry of the Cyclopropyl Group. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987; p 959. (c) Elliott, M.; Janes, N. F. Chem. Soc. Rev. 1978, 7, 473. For recent papers, see: (d) Yoshida, M.; Ezaki, M.; Hashimoto, M.; Yamashita, M.; Shigematsu, N.; Okuhara, M.; Kohsaka, M.; Horikoshi, K. J. Antibiot. 1990, 43, 748. (e) Kuo, M. S.; Zielinski, R. J.; Cialdella, J. I.; Marschke, C. K.; Dupuis, M. J.; Li, G. P.; Kloosterman, D. A.; Spilman, C. H.; Marshall, V. P. J. Am. Chem. Soc. 1995, 117, 10629. (f) Gerwick, W. H.; Proteau, P. J.; Nagle, D. G.; Hamel, E.; Blokhin, A.; Slate, D. L. J. Org. Chem. 1994, 59, 1243. (g) Niwa, H.; Wakamatsu, K.; Yamada, K. Tetrahedron Lett. 1989, 30, 4543. Kigoshi, H.; Niwa, H.; Yamada, K.; Stout, T. J.; Clardy, J. Tetrahedron Lett. 1991, 32, 2427. (h) Baertschi, S. W.; Brash, A. R.; Harris, T. M. J. Am. Chem. Soc. 1989, 111, 5003. (2) For reviews, see: (a) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.; Tanko, J.; Hudlicky, T. Chem. Rev. 1989, 89, 165. (b) Goldschmidt, Z.; Crammer, B. Chem. Soc. Rev. 1988, 17, 229. (c) Paquette, L. A. Chem. Rev. 1986, 86, 733. (d) de Meijere, A.; Wessjohann, L. Synlett 1990, 20. (e) Trost, B. M. In Strain and its implications in Organic Chemistry; de Meijere, A.; Blechert, S., Eds.; Kluwer: Dordrecht, 1989; p 1. (3) (a) Stammer, C. H. Tetrahedron 1990, 46, 2231. (b) Burgess, K.; Ho, K.-K.; Pettitt, B. M. J. Am. Chem. Soc. 1995, 117, 54. (4) (a) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317. (b) He, M.; Dowd, P. J. Am. Chem. Soc. 1996, 118, 711. (c) Mattalia, J.M.; Chanon, M.; Stirling, C. J. M. J. Org. Chem. 1996, 61, 1153. (d) Suckling, C. J. Angew. Chem., Int. Ed. Engl. 1988, 27, 537. (5) For reviews, see: (a) The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; John Wiley and Sons: New York, 1987. (b) The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; John Wiley and Sons: New York, 1995; Vol. 2. (c) Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Ed.; Pergamon: Oxford, 1991; Vol. 4, pp 951-1067. (d) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49. (e) Brookhart, M.; Studabaker, W. B. Chem. Rev. 1987, 87, 411.

struction is based on a selenium-stabilized 1,2-silicon migration process that does not occur with the corresponding sulfur analogues. To enhance the synthetic potential of this [2 + 1] cycloaddition reaction, we are investigating a wide variety of substrates. As part of this effort, electrophilic olefins containing synthetically and potentially biologically useful phosphonate groups were chosen as attractive substrates.7,8 2-Phosphonoacrylates 2 were predicted to have high reactivity toward 1-seleno-2-silylethene 1, since they are isoelectronic analogues of methylenemalonate esters, which have been proven to have effective reactivity toward 1.6b The expected cyclopropanephosphonate ester products are potentially versatile starting materials to access biologically important compounds. For example, R-aminocyclopropanephosphonic acids are of biological interest, in connection with the mimicry of the corresponding amino acids. Although synthesis of the unsubstituted R-aminocyclopropanephosphonic acid has been reported,9 no general synthetic methods for 2-substituted 1-amino-1-cyclopropanephosphonic acids have appeared yet, probably because suitable starting materials are not readily available in the frame of existing methodology. We now wish to disclose the highly efficient [2 + 1] cycloaddition of 1-seleno-2-silylethene 1 to 2-phosphonoacrylates 2a-f leading to the cyclopropanes 310 and the stereoselective synthesis of a new functionalized R-aminocyclopropanephosphonic acid by transformation of adduct 3b. In particular, the electro(6) (a) Yamazaki, S.; Tanaka, M.; Yamaguchi, A.; Yamabe, S. J. Am. Chem. Soc. 1994, 116, 2356. (b) Yamazaki, S.; Tanaka, M.; Inoue, T.; Morimoto, N.; Kumagai, H. J. Org. Chem. 1995, 60, 6546. (c) Yamazaki, S.; Tanaka, M.; Yamabe, S. J. Org. Chem. 1996, 61, 4046. (d) Yamazaki, S.; Kumagai, H.; Takada, T.; Yamabe, S. J. Org. Chem. 1997, 62, 2968. (7) (a) Wadsworth, W. S., Jr. Org. React. 1977, 25, 73. (b) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863. (8) For reviews, see: (a) Engle, R. Chem. Rev. 1977, 77, 349. (b) Kafarski, P.; Lejczak, B. Phosphorus, Sulfur Silicon Relat. Elem. 1991, 63, 193. (c) Kukhar′, V. P.; Svistunova, N. Y.; Soloshonok, V. A. Russ. Chem. Rev. 1993, 62, 261. (9) (a) Erison, M. D.; Walsh, C. T. Biochemistry 1987, 26, 3417. (b) Diel, P. J.; Maier, L. Phosphorus Sulfur 1984, 20, 313. (10) Preminary report: Yamazaki, S.; Imanishi, T.; Moriguchi, Y.; Takada, T. Tetrahedron Lett. 1997, 38, 6397.

S0022-3263(98)00545-3 CCC: $15.00 © 1998 American Chemical Society Published on Web 07/31/1998

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Table 1. [2 + 1] Cycloadditions of 1 with 2-Phosphonoacrylates (2)ain (Eq 2) 2-phosphonoacrylate R1 R2

entry 1 2 3 4 5 6

2a 2b 2c 2d 2e 2f

Me Et t-Bu CH2CH2TMS Et (l)-menthyl

Me Et Me Et iPr Me

time/h

product (yield/%)

3 6 4 4 4 4

3a (96) 3b (95) 3c (52) 3d (66)b 3e (85)c 3f (70)d

tions in the acceptor moiety. We also attempted the reaction of 1 with tetraethyl ethenylidenebis(phosphonate) (6)13 under similar conditions; however, the reaction did not proceed and no cycloadduct was obtained. The carbonyl group of 2 thus seems to exert an important role in this [2 + 1] cycloaddition reaction.

a Reactions were carried out at -78 °C at ∼0.4 M for 1 in CH2Cl2. b 18% recovered 1. c 14% recovered 1. d 12% recovered 1.

philic character of 2 has been investigated in detail. In the synthetic transformations, a selenosilylmethyl group in 3b is employed as aldehyde equivalent via silaPummerer rearrangement and a classical Hofmann rearrangement is also used for introduction of an amino group into the R-aminophosphonic acid. A. [2 + 1] Cycloaddition with 2-Phosphonoacrylates 2-Phosphonoacrylates 2b-f were prepared according to precedented literature procedures from the corresponding phosphonoacetates (eq 1).11 Table 1 summarizes the [2 + 1] cycloaddition reactions of 1 and 2 (eq 2).

Reaction of 1 (1 equiv) and 2-phosphonoacrylates 2a-f (1.3 equiv) was carried out in the presence of SnCl4 (1.5 equiv) in CH2Cl2 at -78 °C for 3-6 h. Quenching with triethylamine (2.6 equiv) gave [2 + 1] cycloadducts 3a-f as single stereoisomeric products in high yields. The increase of the steric bulk in the carboxylate moiety (R1) resulted in somewhat lower yields, although sterically demanding phosphonate ester groups (R2) appear to have less effect of the overall yield (entries 3, 5). The ready formation of cyclopropanes bearing tert-butyl and trimethylsilylethyl protected carboxyl groups 3c and 3d provides suitable handles for further synthetic transformations. No reaction occurred between the donor olefin 1 and the 3-substituted 2-phosphonoacrylates 412 and 5 under these reaction conditions, suggesting steric limita(11) 2a was purchased from Aldrich. (a) Taylor, E. C.; Davies, H. M. L. J. Org. Chem. 1986, 51, 1537. (b)McIntosh, J. M.; Sieler, R. A. Can. J. Chem. 1978, 56, 226. (12) 4 was prepared according to the literature method.11 The stereochemistry of 4 was assigned as E (ca. 90%>). See: (a) Reetz, M. T.; Peter, R.; von Itzstein, M. Chem. Ber. 1987, 120, 121. (b) SainzDı´az, C. I.; Ga´lvez-Ruano, E.; Herna´ndez-Laguna, A.; Bellanato, J. J. Org. Chem. 1995, 60, 74.

The structure of the cyclopropane skeleton of 3a was readily confirmed by the characteristic 1JCH values present in the 13C NMR spectrum (J ) 167 (C2) and 166 (C3) Hz).14 Cyclopropanes 3a-f are all single stereoisomers. A NOE cross peak in the 2D-NOESY spectrum, between H2 and H3a, and the absence of a NOE cross peak between H2 and H3b in cyclopropanes 3a, 3c, and 3f indicated that the CO2R1 and CH(SePh)(SiMe3) groups were cis (Figure 1).15 The stereochemistry of the other cyclopropane products 3b, 3d, and 3e was also assigned as cis from the observed vicinal coupling constants J2,3a. The coupling constants of vicinal protons in cyclopropane rings are characteristic of the stereochemistry, and the J values are in the region of cis-vicinal protons (8.9-9.2 Hz for 3a-f).16

The stereochemical outcome of the products may be explained in terms of a Se- - -C4dO secondary orbital interaction in the first synclinal addition step, as illustrated in Scheme 1.6 Thus, initially a complex of 2 with SnCl4 is formed, which is then attacked by the selenosilyl nucleophile 1. Synclinal stereoselective addition (due to a stabilizing secondary orbital interaction, Se- - -CdO, not Se- - -PO(OR2)2) may cause the observed cis-selectivity regarding CO2R1 and CH(SePh)(SiMe3) groups. Subsequent 1,2-silicon migration from the first produced zwitterion X leads to the second intermediate Y. This is followed by generation of a selenium-bridged intermediate Z by minimum motion; ring closure then affords cyclopropane 3. Thus, single-bond rotation of C1C3 as well as C2-C3 rotation in Z must be a slower process than ring closure. Since the stereochemistry of the original synclinal addition step is retained throughout (13) Degenhardt, C. R.; Burdsall, D. C. J. Org. Chem. 1986, 51, 3488. (14) Stothers, J. B. Carbon-13 NMR Spectroscopy; Academic: New York, 1972. (15) The relative configuration at C2 and C6 was deduced as (R, R) or (S, S) assuming the same stereochemical course as previously discussed.6a,b For 3a and 3c, the combination of large vicinal coupling constants (J2,6 ) 12.5 Hz for 3a/12.7 Hz for 3c), which indicate that ∠H2-C2-C6-H6 is close to 180°, and the observed NOEs (H3b-H13, H5-H10 for 3a/H14-H10 for 3c, and H5-H11,12 for 3a/H14-H11,12 for 3c) supports the above assumption.6b. (16) (a) Williamson, K. L.; Lanford, C. A.; Nicholson, C. R. J. Am. Chem. Soc. 1964, 86, 762. (b) Gey, C.; Perraud, R.; Pierre, J. L.; Cousse, H.; Dussourd D′Hinterland, L.; Mouzin, G. Org. Magn. Reson. 1977, 10, 75. (c) White, J. D.; Jensen, M. S. J. Am. Chem. Soc. 1995, 117, 6224.

Lewis Acid-Promoted Cycloaddition Reactions

J. Org. Chem., Vol. 63, No. 17, 1998 5921 Scheme 1.

a

Proposed Reaction Mechanism for Cyclopropanationa

The carbon atom numbering is the same as that in Figure 1.

gram packages,18 and, as a result, the bidentate structure A was found to be most stable (Figure 2).19

To investigate the electrophilic sites, the frontier orbital LUMO of the bidentate complex A was calculated by STO-3G//LANL2MB. The LUMO shape indicates that the most electrophilic site is the C3 atom and that the

Figure 1. Selected NOEs in the 2D-NOESY spectrum for 3a, 3c, and 3f are indicated. The atom numbering used in the assignment in ref 15 and under Experimental Section is included.

this proposed mechanism, the origin of the observed cis selectivity in 3 arises from a Se-C4 secondary orbital interaction between 2-SnCl4 and 1. To explain the observed stereochemistry, we have carried out ab initio MO calculations for the possible structures of the complex of 2a with SnCl4 by using the LANL2MB method.17 All the ab initio molecular orbital calculations were performed by using Gaussian 94 pro(17) (a) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270. (b) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284. (c) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299.

(18) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G. A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. J. P.; Head-Gordon, M.; Gonzalez, C.; Pople, J. A. Gaussian 94, Revision B.1, Gaussian, Inc., Pittsburgh, PA, 1995. MO calculations using Gaussian 94 were made on the CONVEX SPP1200/XA at the Information Processing Center (Nara University of Education). (19) The geometries of PdO-monocoordinated and CdO-monocoordinated complexes, B and C, were also optimized, but these species were found to be much less stable than A (Figure 2) (in the structure below, energies in square brackets were obtained by ab initio RHF/ LANL2MB calculations and are relative ones to that of the complex A).

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Figure 2. Ab initio RHF/LANL2MB optimized geometries of A, B, C, and 2a. Numbers in parentheses denote atomic net charges of STO-3G//LANL2MB for A, B, C, and 2a. Less stable isomers B and C are described in ref 19.

cofficient of C4 (-0.558) is larger than that of P (-0.114) (Figure 3). The effective overlap with the HOMO of 1 determines the orientation in the synclinal addition step (Scheme 1). 1H, 13C, and 31P NMR spectra of a 2a-SnCl4 complex were measured at low temperature (-58 to -63 °C) (Table 2). A solution of 2a in dichloromethane-d2 was treated with 1.15 equiv of SnCl4 to form a 2a-SnCl4 complex. The change in chemical shift of the carbonyl carbon (C4) in the 13C NMR was +5.8 ppm, which indicates Sn cordination with CdO oxygen. Also, the large downfield shift (144.2 ppm for 2a and 152.9 ppm for 2a-SnCl4) of C3 indicates the significant decrease of electron density on C3 and the resulting enhanced reactivity as an electrophile. A small change in the chemical shift of the phosphonate P atom (+0.5 ppm) was also observed. Although 1H and 13C NMR studies of Lewis acid carbonyl complexation have been investigated in detail,20 31P chemical shift changes by Lewis acid complexation have not been studied systematically.21,22 The small change in going from 2a to 2a-SnCl4 in the (20) (a) Shambayati, S.; Schreiber, S. L. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 1, p 283. (b) Childs, R. F.; Mulholland, D. L.; Nixon, A. Can. J. Chem. 1982, 60, 801.

31

P chemical shift may be related to the difference in the OdP-C angle between 2a (124.6 °) and A (112.4 °) (see Figure 2). Thus, the difference in angle possibly offsets the 31P downfield shift arising from a decrease in electron density due to PdOsSnCl4 complexation.23 Good diastereoselectivity was obtained in the reaction of chiral olefin 2f (entry 6 in Table 1); no diastereoisomer of 3f was detected by NMR analysis. To account for the high diastereoselectivity, attack from the si face with respect to C1 (Scheme 2, vide infra) of the SnCl4coordinated 2f in the addition step is assumed. The LANL2MB-calculated structure of 2f-SnCl4 is shown in Figure 4. In Figure 5, the proposed synclinal approaches (21) 31P NMR spectra of ZnCl2-monocoordination to the phosphoryl oxygen of a ketovinylphosphonate was reported and the chemical shift change ∆δ was +1.8 ppm. McClure C. K.; Hansen, K. B. Tetrahedron Lett. 1996, 37, 2149. (22) 31P NMR spectra of SnCl4-chelated complex of R-acylphosphonate were shifted 1.1-2.4 ppm downfield of free R-acylphosphonate, while 31P of SnCl4-dimeric complex of R-acylphosphonate [(PdO)2SnCl4] were shifted 9.67-8.0 ppm upfield. Telan, L. A.; Poon, C.-D.; Evans, S. A., Jr. J. Org. Chem. 1996, 61, 7455. (23) (a) Gorenstein, D. G. In Phosphorus-31 NMR, Principles and Applications, Gorenstein, D. G., Ed.; Academic Press: London, 1984; p 7. (b) Gorenstein, D. G. Prog. Nucl. Magn. Reson. Spectrosc. 1983, 16, 1.

Lewis Acid-Promoted Cycloaddition Reactions Table 2. 1He

13Ce

31Pf

J. Org. Chem., Vol. 63, No. 17, 1998 5923

NMR Chemical Shifts of Methyl 2-Phosphonoacrylate (2a) and 2a-SnCl4a

(E)-3d,g (Z)-3d,g CO2CH3 PO(OCH3)2 C3d C1d C4d CO2CH3 PO(OCH3)2 P

2a/ppm

2a-SnCl4b/ppm

∆δc/ppm

6.98, JHP ) 42.1 Hz 6.67, JHP ) 20.1 Hz 3.71 3.68, JHP ) 11.4 Hz 144.2 129.8, JCP ) 187 Hz 163.0, JCP ) 16.8 Hz 51.7 52.5, JCP ) 5.3 Hz 16.7

7.58, JHP ) 43.9 Hz 7.17, JHP ) 22.0 Hz 4.12 3.97, JHP ) 11.9 Hz 152.9 121.6, JCP ) 196 Hz 168.8 56.8 56.2, JCP ) 6.1 Hz 17.2

+0.60 +0.50 +0.41 +0.29 +8.7 -8.2 +5.8 +5.1 +3.7 +0.5

a 0.52 M 2a in CD Cl . b 2a-SnCl complex was prepared with 1 equiv of 2a and 1.15 equiv of SnCl which was the same as the 2 2 4 4 standard reaction conditions. c ∆δ ) δ(2a-SnCl4) - δ(2a); positive numbers are downfield shifts. d The atom numbering is the same as e f shown in Scheme 1 and does not follow the IUPAC system. Measured at -58 °C. Measured at -63 °C. g The E/Z stereochemistry of olefin hydrogens was assigned on the basis of the P-H coupling constants.12

Figure 4. Ab initio RHF/LANL2MB optimized geometry of 2f-SnCl4.

Scheme 2

Figure 3. Frontier orbital coefficients of the LUMO of A and HOMO of 1. These coefficients are of STO-3G//LANL2MB.17,18 Bold upward arrows show the most favorable orbital interaction leading to the synclinal-addition path in Scheme 1.

of 1 to 2f-SnCl4 from the si face and re face of C1 are outlined, where C3- - -C2 and C4- - -Se distances are set to ca. 3.0 Å. Approach from the re face of C1 results in the steric repulsion between C6 and the isopropyl carbon of the menthyl group. This proposed diastereoselection is similar to that observed in asymmetric Diels-Alder reactions involving (l)-menthyl acrylates.24 Thus, attack (24) (a) Katagiri, N.; Haneda, T.; Hayasaka, E.; Watanabe, N.; Kaneko, C. J. Org. Chem. 1988, 53, 227. (b) Katagiri, N.; Haneda, T.; Watanabe, N.; Hayasaka, E.; Kaneko, C. Chem. Pharm. Bull. 1988, 36, 3867. (c) Loncharich, R. J.; Schwartz, T. R.; Houk, K. N. J. Am. Chem. Soc. 1987, 109, 14.

from the si side with respect to C1 finally leads to (1S,2S,6S)-3f according to the mechanism shown in Scheme 1 (vide supra). Experimental determination of the absolute stereochemistry of the product 3f is currently under way. This highly efficient [2 + 1] cycloaddition reaction of 1 to 2-phosphonoacrylates 2 may result from the high reactivity of the 2-SnCl4 complex in the addition step

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Figure 6. Frontier orbital coefficients of the LUMO of methyl vinyl ketone-SnCl4 complex (s-cis isomer).25 These coefficients are of STO-3G//LANL2MB.17,18

+0.09585 au and that of methyl vinyl ketone-SnCl4 complex (s-cis isomer) is +0.09324 au, which indicates that both complexes have similar LUMO levels and therefore the HOMO-LUMO gaps between 1 (HOMO level, -0.2289 au) and A or the methyl vinyl ketoneSnCl4 complex are small enough for efficient reaction. On the other hand, the coefficient of C3 is 0.651 in A (2aSnCl4) and much larger than that in methyl vinyl ketone-SnCl4 complex (0.539) (Figure 6). Thus, the localized coefficient of C3 seems to contribute to the highly efficient reaction process, and the role of electrophilic olefins 2a-f becomes clearer. In 2, the phosphonate and carboxylate groups have different functions. The phosphonate group enhances the coefficient of the LUMO at C3 and accordingly the main (C2- - -C3) orbital interaction. On the other hand, the carboxylate group controls the secondary (C4- - -Se) interaction through the large coefficient of LUMO at C4. Without the carboxylate group, i.e. the secondary interaction, we could not obtain the [2 + 1] cycloadduct (i.e. from reaction of 1 and 6). This concept should be useful for the further design of electrophilic olefins in these Lewis acid-mediated reactions. B. Synthetic Application Figure 5. Proposed approaches of 1 to 2f-SnCl4. For the structure of 1, RHF/LANL2MB optimized bond lengths and bond angles are used. For the structure of 2f-SnCl4, RHF/ LANL2MB optimized geometry (Figure 4) is used. C3- - -C2 and C4- - -Se distances are set to 3.0-3.1 Å.

(Scheme 1). The higher reactivity of 2-SnCl4 compared to the corresponding complexes of vinyl ketones with SnCl4, which were originally studied in this [2 + 1] cycloaddition, was examined in terms of both LUMO energy levels and the coefficient of the C3-carbon where the new C-C bond forms in the LUMO of the electophilic olefin-SnCl4 complex.25

The following frontier orbitals were obtained by STO3G//LANL2MB.17,18 The LUMO level of A (2a-SnCl4) is

In the described [2 + 1] cycloadditions with 2-phosphonoacrylates, the observed chemical yields are very high and the resulting highly functionalized cyclopropanephosphonate ester products are potentially versatile starting materials for biologically important compounds. In this context, synthetic application toward novel aminocyclopropanephosphonic acids, which have attracted much attention recently, was attempted.9,26 We have (25) The s-trans isomer of methyl vinyl ketone-SnCl4 complex shown below is 8.7 kcal/mol more unstable than the s-cis isomer by STO-3G//LANL2MB. Therefore, the s-cis isomer is probably the actual electrophile in this reaction.

(26) (a) Hanessian, S.; Cantin, L.-D.; Roy, S.; Andreotti, D.; Gomtsyan, A. Tetrahedron Lett. 1997, 38, 1103. (b) Dappen, M. S.; Pellicciari, R.; Natalini, B.; Monahan, J. B.; Chiorri, C.; Cordi, A. A. J. Med. Chem. 1991, 34, 161. (c) Hanrahan, J. R.; Taylor, P. C.; Errington, W. J. Chem. Soc., Perkin Trans. 1 1997, 493.

Lewis Acid-Promoted Cycloaddition Reactions Scheme 3. Transformation of the Cycloadduct 3b to r-Aminocyclopropanephosphonic Acid 13

J. Org. Chem., Vol. 63, No. 17, 1998 5925

In summary, we have shown that 1-seleno-2-silylethene 1 and 2-phosphonoacrylates 2 undergo SnCl4promoted [2 + 1] cycloaddition reactions stereoselectively in high yields. The phosphonate and carboxylate groups in 2 provide main and secondary charge accepting sites, respectively. The synthetic application of the cyclopropane products resulting in a novel aminocyclopropane phosphonic acid analogue of (Z)-2,3-methanohomoserine was demonstrated. We are currently investigating transformations leading to other aminocyclopropanephosphonic acid derivatives and related biologically interesting compounds. Furthermore, modification of this synthetic approach for asymmetric aminocyclopropanephosphonic acid derivatives utilizing the chiral cyclopropane product 3f is under way in our laboratory.

Experimental Section

carried out transformation of 3b to 1-amino-2-(hydroxymethyl)-1-cyclopropanephosphonic acid (Scheme 3). Thus, 3b was oxidized with NaIO4 in a THF-H2O solution at room temperature to give the sila-Pummerer product 7 in 97% yield.27 The aldehyde 7 was then reduced using NaBH4 in 2-propanol to give the alcohol 8 in 94% yield. Hydrolysis of 8 and subsequent acidification provided γ-lactone 9 in 91% yield.28 The reported synthetic method for (Z)-2,3-methanohomoserine was then employed for transformation of 9 to a protected aminocyclopropanephosphonic acid.29 Treatment of 9 with saturated methanolic ammonia at room temperature and esterification of the resulting alcohol gave amide 10 in 87% yield. Hofmann rearrangement of 10 using lead tetraacetate in refluxing t-BuOH gave 11 in 96% yield.30 Hydrolysis of the acetyl group of 11 gave the alcohol 12 in 100% yield. Deprotection of the N-BOC (N-tertbutoxycarbonyl) group with 1 N HCl in diethyl ether and subsequent deprotection of the phosphonate ester group with iodotrimethylsilane (TMSI) gave 1-amino-2-(hydroxymethyl)-1-cyclopropanephosphonic acid (13) in 64% yield. Thus, stereoselective synthesis of 13, an aminophosphonic acid analogue of (Z)-2,3-methanohomoserine,29 using the cycloadduct 3b as a starting material was achieved. 13 (and intermediates 11 and 12) are potential general precursors of a wide variety of (E)-2-substituted 1-aminocyclopropanephosphonic acids. (27) (a) Reich, H. J.; Shah, S. K. J. Org. Chem. 1977, 42, 1773. (b) Brook, A. G.; Anderson, D. G. Can. J. Chem. 1968, 46, 2115. (c) Carey, F. A.; Hernandez, O. J. Org. Chem. 1973, 38, 2670. (d) Vedejs, E.; Mullins, M. Tetrahedron Lett. 1975, 2017. (28) The synthesis of 3-methyl- and 3,3-dimethylphosphonocyclopropane lactone derivatives was recently reported. Using this method, only trace amounts of 3-unsubstituted derivatives could be obtained. These 3-substituted phosphonocyclopropane lactone derivatives are also promising precursors for 1-aminocyclopropanephosphonic acid derivatives by using the transformations described herein. To¨ke, L.; Ja´szay, Z. M.; Petneha´zy, I.; Clemetis, G.; Vereczkey, G. D.; Ko¨vesdi, I.; Rockenbauer, A.; Kova´ts, K. Tetrahedron 1995, 51, 9167. (29) (a) Pirrung, M. C.; Dunlap, S. E.; Trinks, U. P. Helv. Chim. Acta 1989, 72, 1301. (b) Aitken, D. J.; Royer, J.; Husson, H.-P. J. Org. Chem. 1990, 55, 2814. (c) Burgess, K.; Ho, K.-K. J. Org. Chem. 1992, 57, 5931. (d) Koskinen, A. M. P.; Mun˜oz, L. J. Org. Chem. 1993, 68, 879. (30) Baumgarten, H. E.; Staklis, A. J. Am. Chem. Soc. 1965, 87, 1141.

General Methods. Melting points are uncorrected. IR spectra were recorded in the FT-mode. 1H NMR spectra were recorded at 200, 400, 500, or 600 MHz. 13C NMR spectra were recorded at 50.1, 100.6, 125.7, or 150.8 MHz. Chemical shifts are reported in parts per million relative to Me4Si or residual nondeuterated solvent. 13C chemical shift in D2O is relative to dioxane as internal reference. 31P NMR spectra were recorded at 161.9 or 202.4 MHz. 31P chemical shifts are relative to 85% H3PO4. Mass spectra were recorded at an ionizing voltage of 70 eV by EI or FAB. All reactions were carried out under a nitrogen atmosphere. Preparation of 2-Phosphonoacrylates. 2-Phosphonoacrylates 2b-f were prepared according to literature procedures from the corresponding phosphonoacetates.11 (l)-Menthyl2-(Dimethylphosphono)acrylate(2f). Paraformaldehyde (1.18 g, 39.2 mmol) was dissolved in methanol (58 mL) containing piperidine (0.116 mL, 1.18 mmol) by refluxing the solution for 0.5 h. (l)-Menthyl 2-(dimethylphosphono)acetate (5.73 g, 18.7 mmol) was added and the solution was heated at reflux for 19 h. After evaporation of the methanol, the residue was dissolved in toluene (55 mL). p-Toluenesulfonic acid (32 mg, 0.187 mmol) was added and the mixture was refluxed under a Dean-Stark water separator for 8 h. The solvent was removed and the residue purified by column chromatography over silica gel eluting with CH2Cl2ether (1:1) to give 2f (3.68 g, 68%) (Rf 0.6). 2f: colorless oil; 1 H NMR (200 MHz, CDCl3) δ (ppm) 0.766 (d, J ) 6.8 Hz, 3 H), 0.908 (d, J ) 7.1 Hz, 3 H), 0.916 (d, J ) 6.4 Hz, 3 H), 0.841.18 (m, 3 H), 1.39-1.73 (m, 4 H), 1.86-2.10 (m, 2 H), 3.81 (d, JHP ) 10 Hz, 6 H), 4.81 (ddd, J ) 10.9, 4.4, 4.4 Hz, 1 H), 6.76 (d, JHP ) 20.5 Hz, 1 H), 7.12 (d, JHP ) 42.5 Hz, 1 H); 13C NMR (50.1 MHz, CDCl3) δ (ppm) 15.11, 19.79, 20.98, 22.30, 24.98, 30.44, 33.19, 39.67, 46.09, 51.96, 74.50, 131.8 (d, JCP ) 186 Hz), 142.4, 162.0 (d, JCP ) 16 Hz); IR (neat) 2960, 2872, 1721, 1609, 1263 cm-1; MS (EI), m/z 318; exact mass M+ 318.1613 (calcd for C15H27O5P 318.1596); [R]D16.4 -66.8° (c ) 1.0, CHCl3). tert-Butyl 2-(Dimethylphosphono)acrylate (2c). Yield 48% (Rf 0.5 (CH2Cl2:ether ) 2:1)): pale yellow oil; 1H NMR (200 MHz, CDCl3) δ (ppm) 1.53 (s, 9 H), 3.78 (s, 3 H), 3.84 (s, 3 H), 6.71 (dd, JHP ) 20.8 Hz, JHH ) 1.7 Hz, 1 H), 7.14 (dd, JHP ) 42.7 Hz, JHH ) 1.7 Hz, 1 H); 13C NMR (50.1 MHz, CDCl3) δ (ppm) 27.58, 52.63, 52.75, 82.03, 133.2 (d, JCP ) 185 Hz), 142.6 (d, JCP ) 5.9 Hz), 162.3 (d, JCP ) 16 Hz); IR (neat) 2982, 2960, 2856, 1717, 1607, 1259 cm-1; MS (FAB) m/z 237 (MH+); Anal. Calcd for C9H17O5P: C, 45.76; H, 7.35. Found: C, 45.86; H, 7.34. Isopropyl 2-(Diethylphosphono)acrylate (2e). Yield ca. 67% (including a small amount of impurity) (Rf ) 0.6 (CH2Cl2: ether ) 2:1)): pale yellow oil; 1H NMR (200 MHz, CDCl3) δ (ppm) 1.29-1.38 (m, 17 H), 4.29 (q, J ) 7.1 Hz, 2 H), 4.684.85 (m, 2 H), 6.76 (dd, JHP ) 20.4 Hz, JHH ) 1.9 Hz, 1 H), 6.98 (dd, JHP ) 41.8 Hz, JHH ) 1.9 Hz, 1 H); 13C NMR (50.1 MHz, CDCl3) δ (ppm) 13.36, 22.94, 23.05, 23.29, 23.34, 60.52, 70.44, 70.56, 133.7 (d, JCP ) 186 Hz), 142.0 (d, JCP ) 4.4 Hz),

5926 J. Org. Chem., Vol. 63, No. 17, 1998 163.0 (d, JCP ) 16 Hz); IR (neat) 2984, 2940, 2880, 1725, 1609, 1259 cm-1; MS (FAB) m/z 265 (MH+). 1-Ethyl 4-Methyl 2-(Diethoxyphosphoryl)butanedioate. Sodium hydride (1.18 g, 60% dispersion in oil, 29.4 mmol, washed 3 times with pentane) was suspended in freshly distilled THF (26.8 mL). After the mixture was cooled to 0 °C, triethyl phosphonoacetate (6.0 g, 26.8 mmol) was added dropwise over 10 min. After 1 h, methyl bromoacetate (4.10 g, 26.8 mmol) was added, and the mixture was stirred for 12 h at 20 °C. The mixture was extracted with ether and the ether extracts were washed with 1 N hydrochloric acid and saturated sodium chloride solution and dried (MgSO4). The solvent was evaporated in vacuo. The residue was purified by column chromatography over silica gel eluting with CH2Cl2ether (4:1) to give the title compound (4.00 g, 76%) (Rf 0.5): colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 1.26-1.37 (m, 9 H), 2.82 (ddd, J ) 17.8, 9.2, 3.6 Hz, 1 H), 3.08 (ddd, J ) 17.8, 11.1, 6.9 Hz, 1 H), 3.46 (ddd, J ) 24.0, 11.1, 3.6 Hz, 1 H), 3.70 (s, 3 H), 4.09-4.26 (m, 6 H); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 13.86, 16.07, 16.12, 16.17, 31.09 (d, JCP ) 2.3 Hz), 41.15 (d, JCP ) 132.0 Hz), 51.90, 61.53, 62.76, 62.82, 168.0 (d, JCP ) 5.3 Hz), 171.4 (d, JCP ) 18.3 Hz); IR (neat) 2986, 1736, 1259 cm-1; MS (EI) m/z 296; exact mass M+ 296.0998 (calcd for C11H21O7P 296.1025). 1-Ethyl 4-Methyl 2-(Diethoxyphosphoryl)-2-(phenylseleno)butanedioate. Sodium hydride (0.688 g, 60% dispersion in oil, 16.7 mmol) was washed 3 times with pentane and suspended in freshly distilled THF (20.9 mL). After the mixture was cooled to 0 °C, 1-ethyl 4-methyl 2-(diethoxyphosphoryl)butanedioate (3.65 g, 9.56 mmol) in THF (2.4 mL) was added dropwise and the mixture was stirred for 2 h at 20 °C. Phenylselenyl bromide [11.5 mmol, prepared by adding bromine (0.31 mL, 962 mg, 6.02 mmol) to a stirred solution of diphenyl diselenide (1.80 g, 5.72 mmol) in THF (16.1 mL) at 20 °C followed by further stirring for 10 min] was then added. The mixture was stirred for 12 h at 20 °C and 1 N HCl and dichloromethane were added to the mixture. The organic layer was separated, washed with saturated sodium bicarbonate solution, and dried (MgSO4). The solvent was evaporated in vacuo. The residue was purified by column chromatography over silica gel eluting with CH2Cl2-ether (2:1) to give the title compound (2.92 g, 68%) (Rf 0.6): pale yellow oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 1.25 (t, J ) 7.1 Hz, 3 H), 1.31-1.38 (m, 6 H), 2.67 (dd, J ) 17.2, 17.1 Hz, 1 H), 3.19 (dd, J ) 17.2, 7.1 Hz, 1 H), 3.61 (s, 3 H), 4.14-4.23 (m, 4 H), 4.25-4.41 (m, 2 H), 7.29-7.33 (m, 2 H), 7.39-7.43 (m, 1 H), 7.76-7.79 (m, 2 H); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 13.91, 16.37, 16.43, 16.51, 37.84, 47.38 (d, JCP ) 144 Hz), 51.79, 62.28, 63.59 (JCP ) 7.6 Hz), 65.03 (d, JCP ) 6.9 Hz), 126.3, 128.8, 130.0, 138.8, 168.6, 169.7 (d, JCP ) 13.0 Hz); IR (neat) 2986, 1729, 1253 cm-1; MS (EI) m/z 452; exact mass M+ 452.0482 (calcd for C17H25O7PSe 452.0503). 1-Ethyl 4-Methyl (E)-2-(Diethoxyphosphoryl)-2-butenedioate (5). Hydrogen peroxide (30%, 4.64 g) and water (0.97 mL) were added to a stirred solution of 1-ethyl 4-methyl 2-(diethoxyphosphoryl)-2-(phenylseleno)butanedioate (2.69 g, 5.97 mmol) in dichloromethane (28.1 mL) at such a rate the temperature remained above 30 °C. After being stirred for a further 1 h at 20 °C, the mixture was washed with saturated sodium bicarbonate solution and dried over MgSO4, and the solvent was evaporated in vacuo. The residue was purified by column chromatography over silica gel eluting with CH2Cl2ether (2:1) to give 5 (1.223 g, ca. 79%) (Rf 0.6). (A small amount of unidentified inpurity was present). 5: pale yellow oil; 1H NMR (500 MHz, CDCl3) δ (ppm) 1.33-1.38 (m, 9 H), 3.79 (s, 3 H), 4.14-4.21 (m, 4 H), 4.34 (q, J ) 7.2 Hz, 2 H), 6.81 (d, JHP ) 22.0 Hz, 1 H); 13C NMR (125.7 MHz, CDCl3) δ (ppm) 13.96, 16.16, 16.21, 52.49, 62.18, 63.46 (d, JCP ) 5.2 Hz), 135.1 (d, JCP ) 7.3 Hz), 139.1 (JCP ) 172 Hz), 163.9 (JCP ) 25.9 Hz), 164.4 (JCP ) 11.4 Hz); 31P NMR (202.4 MHz, CDCl3) δ (ppm) 11.1; IR (neat) 2960, 2872, 1721, 1607, 1263 cm-1; MS (FAB) m/z 295 (MH+). A Typical Experimental Procedure in Table 1 (Entry 1). To a solution of 1 (256 mg, 1.00 mmol) in dichloromethane (2.5 mL) was added SnCl4 (0.176 mL, 391 mg, 1.50 mmol),

Yamazaki et al. followed by 2-phosphonoacrylate (2a) (0.202 mL, 252 mg, 1.30 mmol) at -78 °C. The mixture was stirred at -78 °C for 3 h. The reaction mixture was quenched by triethylamine (0.36 mL, 260 mg, 2.6 mmol) and then saturated aqueous NaHCO3. The mixture was extracted with dichloromethane and the organic phase was washed with water, dried (Na2SO4), and evaporated in vacuo. The residue was purified by column chromatography over silica gel eluting with CH2Cl2-ether (2:1) to give 3a (430 mg, 96%) (Rf 0.3). Methyl r-1-(Dimethoxyphosphoryl)-c-2-[(phenylseleno)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (3a): pale yellow oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 0.105 (s, 9 H, H13), 1.61 (ddd, J ) 9.9, 7.7, 4.5 Hz, 1 H, H3b), 1.86 (ddd, J ) 14.2, 9.0, 4.5 Hz, 1 H, H3a), 2.24 (dddd, J ) 14.1, 12.5, 9.0, 7.7 Hz, 1 H, H2), 2.59 (d, J ) 12.5 Hz, 1 H, H6), 3.40 (s, 3 H, H5), 3.80 (d, J ) 11.0 Hz, 3 H, H7), 3.89 (d, J ) 11.0 Hz, 3 H, H8), 7.19-7.24 (m, 3 H, H11,12), 7.48-7.52 (m, 2 H, H10) (see numbering in Figure 1); Observed NOEs in the 2DNOESY spectrum were H2-H3a, H2-H6, H2-H13, H3a-H3b, H3b-H6, H3b-H13, H5-H6, H5-H10, H5-H11,12, H6-H10, H6H13, H10-H11, H10-H13; 1H assignments were determined by H-H COSY and NOESY; 13C NMR (50.1 MHz, CDCl3) δ (ppm) -2.114 (JCH ) 120 Hz, C13), 23.69 (JCH ) 166 Hz, C3), 25.10 (d, JCP ) 190.5 Hz, C1), 28.69 (d, JCH ) 152 Hz, C6), 33.19 (JCH ) 167, 10 Hz, C2), 52.37 (JCH ) 148 Hz, C5), 53.24 (d, JCP ) 5.9 Hz, JCH ) 148 Hz, C7 or 8), 53.36 (d, JCP ) 5.9 Hz, JCH ) 148 Hz, C7 or 8), 126.9 (JCH ) 161, 7.3 Hz, C12), 128.6 (JCH ) 160, 5.1 Hz, C10 or 11), 130.3 (C9), 133.5 (JCH ) 161 Hz, C10 or 11), 168.5 (d, JCP ) 7.3 Hz, C4) (see numbering in Figure 1); IR (neat) 2956, 1721, 1578, 1251 cm-1; MS (EI) m/z 450; exact mass M+ 450.0536 (calcd for C17H27O5PSeSi 450.0530). Ethyl r-1-(diethoxyphosphoryl)-c-2-[(phenylseleno)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (3b) (Rf 0.5 (CH2Cl2:ether ) 2:1)): pale yellow oil; 1H NMR (200 MHz, CDCl3) δ (ppm) 0.079 (s, 9 H), 1.15 (t, J ) 7.1 Hz, 3 H), 1.32 (t, J ) 7.1 Hz, 3 H), 1.38 (t, J ) 7.1 Hz, 3 H), 1.60 (ddd, J ) 9.8, 7.3, 4.4 Hz, 1 H), 1.85 (ddd, J ) 13.8, 9.2, 4.4 Hz, 1 H), 2.10-2.32 (m, 1 H), 2.61 (d, J ) 12.5 Hz, 1 H), 3.70 (dq, J ) 10.7, 7.1 Hz, 1 H), 3.96 (dq, J ) 10.7, 7.1 Hz, 1 H), 4.094.31 (m, 4 H), 7.19-7.29 (m, 3 H), 7.49-7.52 (m, 2 H); 13C NMR (50.1 MHz, CDCl3) δ (ppm) -1.909, 13.92, 16.37, 16.52, 23.84, 25.96 (d, JCP ) 189 Hz), 28.72, 32.89, 61.51, 62.65 (d, JCP ) 5.9 Hz), 126.9, 128.7, 130.7, 133.6, 168.5 (d, JCP ) 7.3 Hz); IR (neat) 2984, 2908, 1717, 1578, 1251 cm-1; MS (EI) m/z 492. Anal. Calcd for C20H33O5PSeSi: C, 48.88; H, 6.77. Found: C, 48.68; H, 6.78. tert-Butyl r-1-(Dimethoxyphosphoryl)-c-2-[(phenylseleno)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (3c) (Rf 0.5 (CH2Cl2:ether ) 2:1)): colorless oil; 1H NMR (600 MHz, CDCl3) δ (ppm) -0.013 (s, 9 H, H13), 1.43 (s, 9 H, H14), 1.59 (ddd, J ) 10.0, 7.6, 4.5 Hz, 1 H, H3b), 1.84 (ddd, J ) 14.1, 9.0, 4.5 Hz, 1 H, H3a), 2.11 (dddd, J ) 14.2, 12.7, 9.0, 7.6 Hz, 1 H, H2), 2.66 (d, J ) 12.7 Hz, 1 H, H6), 3.81 (d, J ) 11.0 Hz, 3 H, H7), 3.86 (d, J ) 11.0 Hz, 3 H, H8), 7.18-7.21 (m, 3 H, H11,12), 7.50-7.52 (m, 2 H, H10) (see numbering in Figure 1); observed NOEs in the 2D-NOESY spectrum were H2-H3a, H2-H10, H2-H13, H3a-H3b, H3b-H6, H3b-H13, H6-H13, H6-H14, H7-H14, H8-H14, H10-H11,12, H10-H13, H10-H14, H11,12-H13, H11,12-H14; 13C NMR (150.8 MHz, CDCl3) δ (ppm) 1.818 (C13), 23.43 (d, JCP ) 2.7 Hz, C3), 26.25 (d, Jcp ) 188 Hz, C1), 27.40 (C6), 28.05 (C14), 31.16 (d, JCP ) 2.1 Hz, C2), 53.19 (Jcp ) 6.9 Hz, C7), 53.30 (JCP ) 5.7 Hz, C8), 82.46 (C5), 126.9 (C12), 128.8 (C11), 130.2 (C9), 133.4 (C10), 167.1 (d, JCP ) 6.3 Hz, C4); 1H and 13C assignments were determined by NOESY, HMQC, and HMBC spectra; IR (neat) 2958, 1715, 1578, 1251 cm-1; MS (EI) m/z 492; exact mass M+ 492.0992 (calcd for C20H33O5PSeSi 492.1000). (2-Trimethylsilyl)ethyl r-1-(Diethoxyphosphoryl)-c-2[(phenylseleno)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (3d) (Rf 0.65 (CH2Cl2:ether ) 4:1)): colorless oil; 1H NMR (200 MHz, CDCl ) δ (ppm) -0.032 (s, 9 H), 0.087 (s, 3 9 H), 0.847-0.953 (m, 2 H), 1.33 (t, J ) 7.1 Hz, 3 H), 1.39 (t, J ) 7.1 Hz, 3 H), 1.60 (ddd, J ) 9.8, 7.6, 4.5 Hz, 1 H), 1.84 (ddd, J ) 13.9, 9.1, 4.5 Hz, 1 H), 2.09-2.31 (m, 1 H), 2.63 (d, J ) 12.5 Hz, 1 H), 3.68-3.98 (m, 2 H), 4.10-4.35 (m, 4 H),

Lewis Acid-Promoted Cycloaddition Reactions 7.18-7.22 (m, 3 H), 7.47-7.52 (m, 2 H); 13C NMR (50.1 MHz, CDCl3) δ (ppm) -1.909, -1.646, 16.40, 16.52, 17.22, 23.78, 26.00 (d, JCP ) 188 Hz), 28.57, 32.89, 62.66 (d, JCP ) 7.3 Hz), 63.87, 126.9, 128.7, 130.8, 133.4, 168.6 (d, JCP ) 7.3 Hz); IR (neat) 2956, 2904, 1715, 1578, 1251 cm-1; MS (EI) m/z 564; exact mass M+ 564.1430 (calcd for C23H41O5PSeSi2 564.1395). Ethyl r-1-(Diisopropoxyphosphoryl)-c-2-[(phenylseleno)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (3e) (Rf 0.6 (CH2Cl2: ether ) 2:1)): colorless oil; 1H NMR (200 MHz, CDCl3) δ (ppm) 0.053 (s, 9 H), 1.18 (t, J ) 7.1 Hz, 3 H), 1.28-1.41 (m, 12 H), 1.58 (ddd, J ) 9.8, 7.4, 4.3 Hz, 1 H), 1.85 (ddd, J ) 13.6, 9.0, 4.3 Hz, 1 H), 2.05-2.26 (m, 1 H), 2.58 (d, J ) 12.5 Hz, 1 H), 3.78 (dd, J ) 10.8, 7.1 Hz, 1 H), 3.97 (dd, J ) 10.8, 7.2 Hz, 1 H), 4.66-4.88 (m, 2 H), 7.19-7.22 (m, 3 H), 7.50-7.55 (m, 2 H); 13C NMR (50.1 MHz, CDCl3) δ (ppm) -1.880, 13.95, 23.99, 24.05, 24.13, 26.81 (d, JCP ) 189 Hz), 28.60, 32.46, 61.42, 70.97 (d, JCP ) 5.9 Hz), 71.07 (d, JCP ) 4.4 Hz), 126.9, 128.7, 130.7, 133.7, 168.8 (d, JCP ) 5.9 Hz); IR (neat) 2980, 1715, 1578, 1251 cm-1; MS (EI) m/z 520; exact mass M+ 520.1306 (calcd for C22H37O5PSeSi 520.1314). (l)-Menthyl r-1-(Dimethoxyphosphoryl)-c-2-[(phenylseleno)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (3f) (Rf 0.75 (CH2Cl2:ether ) 2:1)): colorless crystals; mp 7476 °C (hexane); 1H NMR (400 MHz, CDCl3) δ (ppm) -0.038 (s, 9 H, H13), 0.482 (d, J ) 7.0 Hz, 3 H, H14), 0.822 (d, J ) 7.1 Hz, 3 H), 0.910 (d, J ) 6.6 Hz, 3 H), 0.776-1.07 (m, 3 H), 1.391.51 (m, 2 H), 1.61-1.68 (m, 3 H, including H3b), 1.90 (ddd, J ) 14.3, 8.9, 4.3 Hz, H3a), 2.08-2.23 (m, 3 H, including H2), 2.65 (d, J ) 12.8 Hz, 1 H, H6), 3.81 (d, J ) 10.8 Hz, 3 H, H7), 3.85 (d, J ) 10.8 Hz, 3 H, H8), 4.68 (ddd, J ) 10.8, 10.8, 4.5 Hz, 1 H, H5), 7.18-7.21 (m, 3 H, H11,12), 7.51-7.54 (m, 2 H, H10); selected observed NOEs in the 2D-NOESY spectrum were H2-H3a, H2-H6, H2-H13, H3a-H3b, H3b-H6, H3b-H13, H6-H10, H6-H13, and H10-H14; 13C NMR (100.6 MHz, CDCl3) δ (ppm) -1.673 (CH3, JCH ) 119 Hz, C13), 16.17 (CH3, JCH ) 124 Hz, C14), 21.11, 22.10, 23.07, 24.12 (Jcp ) 3.1 Hz, C3), 25.58, 25.83 (d, JCP ) 190 Hz, C1), 27.40 (C6), 31.46 (CH, JCP ) 2.3 Hz, JCH ) 161 Hz, C2), 31.50 (CH, JCH ) 123 Hz), 34.29 (CH2, JCH ) 126 Hz), 40.68 (CH2, JCH ) 125 Hz), 47.22 (CH, JCH ) 125 Hz), 53.34 (CH, JCP ) 8.4 Hz, JCH ) 148 Hz, C8), 53.42 (CH, JCP ) 6.9 Hz, JCH ) 148 Hz, C7), 76.05 (CH, C6), 127.2 (CH, JCH ) 161, 7.3 Hz, C12), 128.9 (CH, JCH ) 160 Hz, C11), 130.1 (C, C9), 134.1 (CH, JCH ) 164 Hz, C10), 168.1 (C, JCP ) 6.9 Hz, C4); nondecoupling spectrum was measured at 50.1 MHz and carbon multiplicity was only partially assigned because of complexity; partial 1H and 13C assignments were also determined by COSY, NOESY, HMQC, and TOCSY spectra; IR (KBr) 2960, 2872, 1705, 1578, 1257 cm-1; MS (EI) m/z 574; exact mass M+ 574.1808 (calcd for C26H43O5PSeSi 574.1783). Anal. Calcd for C26H43O5PSeSi: C, 54.44; H, 7.56. Found: C, 54.42; H, 7.51; [R]D22.5 -42.3° (c ) 1.0, CHCl3). Ethyl r-1-(Diethoxyphosphoryl)-c-2-formyl-1-cyclopropanecarboxylate (7). To a solution of 3b (491 mg, 1.0 mmol) in THF (20 mL) and water (10 mL) was added NaIO4 (1.07 g, 5.0 mmol) with vigorous stirring. The mixture was stirred for 4.5 h at room temperature (22 °C). The reaction mixture was concentrated in vacuo and poured into ether (100 mL) and saturated aqueous NaHCO3 solution (50 mL). The organic layer was separated. The water layer was extracted with additional ether (100 mL × 5). The combined organic layer was washed with water, dried (MgSO4), and concentrated in vacuo to give 7 (270 mg, 97%) (Rf 0.4 (ether:methanol ) 19: 1)). 7: pale yellow oil; 1H NMR (200 MHz, CDCl3) δ (ppm) 1.30 (t, J ) 7.2 Hz, 3 H), 1.35 (t, J ) 7.1 Hz, 6 H), 1.91 (ddd, J ) 14.7, 8.7, 5.0 Hz, 1 H), 2.15 (ddd, J ) 12.0, 6.6, 5.0 Hz, 1 H), 2.57 (dddd, J ) 12.2, 8.7, 6.6, 5.1 Hz, 1 H), 4.11-4.30 (m, 6 H), 9.29 (d, J ) 5.1 Hz, 1 H); 13C NMR (50.1 MHz, CDCl3) δ (ppm) 13.83, 16.11, 16.22, 16.89, 29.26 (d, JCP ) 183 Hz), 32.43 (d, JCP ) 2.9 Hz), 62.24, 63.11 (d, JCP ) 5.9 Hz), 63.23 (d, JCP ) 5.9 Hz), 166.2 (d, JCP ) 4.4 Hz), 196.6; IR (neat) 2988, 1729, 1257 cm-1; MS (EI) m/z (relative intensity) 279 (5.4, M + 1), 263 (5.4), 233 (25), 205 (100); MS (FAB) m/z 279 (MH+). Ethyl r-1-(Diethoxyphosphoryl)-c-2-hydroxymethyl-1cyclopropane carboxylate (8). To a solution of 7 (653 mg, 2.35 mmol) in iPrOH (13.4 mL) was added NaBH4 (36 mg, 0.94

J. Org. Chem., Vol. 63, No. 17, 1998 5927 mmol) in three portions at -78 °C. The mixture was stirred for 2 h at -78 °C. Saturated aqueous Na2SO4 solution (2 mL) was added to the reaction mixture. The mixture was extracted with ether (60 mL × 5). The organic phase was dried (MgSO4) and evaporated in vacuo to give 8 (622 mg, 94%) (Rf 0.4 (ether: methanol ) 19:1)). 8: pale yellow oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 1.31 (t, J ) 7.1 Hz, 3 H), 1.32-1.37 (m, 6 H), 1.47 (ddd, J ) 10.4, 7.1, 4.8 Hz, 1 H), 1.60 (ddd, J ) 14.3, 8.9, 4.8 Hz, 1 H), 1.73 (brs, 1 H), 2.13 (m, 1 H), 3.48 (dd, J ) 12.0, 9.0 Hz, 1 H), 3.96 (dd, J ) 12.0 Hz, 5.0 Hz, 1 H), 4.13-4.23 (m, 4 H), 4.25 (q, J ) 7.1 Hz, 2 H); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 14.11, 16.23 (d, JCP ) 3.1 Hz), 16.36, 16.42, 25.01 (d, JCP ) 188 Hz), 28.09 (d, JCP ) 3.1 Hz), 60.99, 61.94, 62.79 (d, JCP ) 6.1 Hz), 62.92 (d, JCP ) 6.1 Hz), 168.6 (d, JCP ) 6.9 Hz); IR (neat) 3400, 2986, 2918, 1725, 1232 cm-1; MS (EI) m/z 280; exact mass M+ 280.1107 (calcd for C11H21O6P 280.1076). Diethyl 3-Oxabicyclo[3.1.0]hexan-2-one-1-phosphonate (9). To a solution of 8 (756 mg, 2.7 mmol) in EtOH (2.5 mL) was added dropwise a 50% (wt %) aqueous NaOH solution (237 µL) at 0 °C. The resulting solution was stirred for 2 h at 55 °C and then for 0.5 h at 18 °C. The EtOH was evaporated, and the remaining solution was diluted with water (1 mL). The aqueous phase was acidified with KHSO4 and extracted with Et2O twice. The combined organic extracts were dried (MgSO4) and evaporated to give 9 (577 mg, 91%) (Rf 0.2 (ether: methanol ) 19:1)). 9: pale yellow oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 1.31 (ddd, J ) 10.4, 4.9, 4.9 H, 1 H), 1.37 (t, J ) 7.4 Hz, 3 H), 1.39 (t, J ) 7.4 Hz, 3 H), 1.88 (ddd, J ) 15.3, 7.8, 4.9 Hz, 1 H), 2.77 (dddd, J ) 10.1, 7.8, 4.9, 4.9 Hz, 1 H), 4.20-4.31 (m, 5 H), 4.40 (dd, J ) 9.5, 4.9 Hz, 1 H); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 16.22, 16.28, 17.63 (d, JCP ) 3.1 Hz), 22.57 (d, JCP ) 209 Hz), 24.66 (d, JCP ) 1.5 Hz), 63.64 (d, JCP ) 6.9 Hz), 63.66 (d, JCP ) 6.1 Hz), 67.73 (d, JCP ) 3.1 Hz), 171.5 (d, JCP ) 11 Hz); IR (neat) 2988, 2918, 1773, 1255 cm-1; MS (EI) m/z 234; exact mass M+ 234.0673 (calcd for C9H15O5P 234.0658). c-2-(Acetoxymethyl)-r-1-(diethoxyphosphoryl)-1-cyclopropanecarboamide (10). The lactone 9 (640 mg, 2.73 mmol) was dissolved in methanol (10 mL), and methanol saturated with ammonia (ca. 5.8 M, 5.0 mL, 29 mmol) were added and the solution stirred for 17 h at room temperature. The solvent was the evaporated in vacuo and the residue dissolved in dry CH2Cl2 (10 mL) and cooled to 0 °C, and triethylamine (326 mg, 3.27 mmol) and (dimethylamino)pyridine (20 mg) were added to the solution, followed by dropwise addition of acetic anhydride (334 mg, 3.27 mmol). After stirring for 4 h at 0 °C, water was added and the solution was extracted with CH2Cl2. The organic layers were dried (Na2SO4) and evaporated. The residue was purified by column chromatography over silica gel eluting with ether-methanol (19:1) to give 10 (698 mg, 87%) (Rf 0.3 (ether:methanol ) 19: 1)). 10: colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 1.321.39 (m, 6 H), 1.43 (ddd, J ) 14.1, 9.2, 4.8 Hz, 1 H), 1.73 (ddd, J ) 10.1, 7.0, 4.8 Hz, 1 H), 2.05 (s, 3 H), 2.03-2.14 (m, 1 H), 3.96 (dd, J ) 11.8, 8.9 Hz, 1 H), 4.11-4.24 (m, 4 H), 4.37 (ddd, J ) 11.8, 6.0, 1.2 Hz, 1 H), 5.68 (brs, 1 H), 7.37 (brs, 1 H); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 14.40 (JCP ) 3.1, JCH ) 166 Hz, CH2), 16.31 (JCP ) 6.1, JCH ) 127 Hz, CH3), 16.36 (JCP ) 5.3, JCH ) 127 Hz, CH3), 20.76 (JCH ) 129 Hz, CH3), 24.19 (JCP ) 2.3, JCH ) 167 Hz, CH), 24.90 (JCP ) 181 Hz, C), 62.25 (JCP ) 1.5, JCH ) 150 Hz, CH2), 63.06 (JCP ) 6.1, JCH ) 148 Hz, CH2), 63.23 (JCP ) 6.9, JCH ) 149 Hz, CH2), 167.2 (JCP ) 9.2 Hz, C), 170.7 (C); IR (neat) 3468, 3202, 2988, 1742, 1676, 1615, 1241 cm-1; MS (EI) m/z 293; exact mass M+ 293.1046 (calcd for C11H20O6NP 293.1029). Diethyl t-2-(Acetoxymethyl)-r-1-[N-(tert-butoxycarbonyl)amino]-1-cyclopropanephosphonate (11). A solution of 10 (110 mg, 0.375 mmol) and t-BuOH (1.9 mL) was heated to 70 °C. Lead tetraacetate (665 mg, 1.50 mmol) was added and the mixture was heated at reflux for 5 h. After cooling to room temperature, ether (0.9 mL) followed by NaHCO3 (60 mg) were added, and the mixture was stirred for 10 min. The mixture was filtered through a short plug of silica gel and the filtrate evaporated. The residue was purified by column chromatog-

5928 J. Org. Chem., Vol. 63, No. 17, 1998 raphy over silica gel eluting with ether-methanol (19:1) to give 11 (132 mg, 96%) (Rf 0.5 (ether:methanol ) 19:1)). 11: colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 1.18 (ddd, J ) 13.5, 6.8, 6.8 Hz, 1 H), 1.29-1.35 (m, 6 H), 1.45 (s, 9 H), 1.69-1.76 (m, 1 H), 1.78-1.85 (m, 1 H), 3.98 (dd, J ) 11.5, 9.6 Hz, 1 H), 4.09-4.25 (m, 4 H), 4.35 (dd, J ) 11.5, 2.8 Hz, 1 H), 5.45 (brs, 1 H); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 16.38, 16.38, 16.50 (d, JCP ) 6.1 Hz), 20.97, 21.80, 28.36, 30.71 (d, JCP ) 221 Hz), 62.45 (d, JCP ) 6.9 Hz), 62.64, 63.02 (d, JCP ) 4.7 Hz), 80.04, 155.7, 171.2; IR (neat) 3252, 2984, 2936, 1735, 1721, 1241 cm-1; MS (EI) m/z 365; exact mass M+ 365.1614 (calcd for C15H28O7NP 365.1604). Diethyl r-1-[N-(tert-Butoxycarbonyl)amino]-t-2-(hydroxymethyl)-1-cyclopropanephosphonate (12). Potassium carbonate (276 mg, 2.0 mmol) was added to a stirred solution of 11 (365 mg, 1.0 mmol) in MeOH (5.6 mL). After the mixture had been heated at 70 °C for 17 h, the MeOH was evaporated, water was added to the residue, and the resulting solution was extracted with ether. The organic layer was dried (MgSO4), and the solvent was evaporated to give 12 (324 mg, 100%). 12: colorless oil; 1H NMR (400 MHz, CDCl3) δ (ppm) 0.632 (ddd, JPC ) 12.8, JHH ) 6.4, 6.4 Hz, 1 H), 1.30-1.36 (m, 6 H), 1.41-1.49 (m, 1 H), 1.45 (s, 9 H), 1.82 (brs, 1 H), 2.052.12 (m, 1 H), 3.17 (dd, J ) 11.9, 11.3 Hz, 1 H), 4.00 (bd, J ) 11.9 Hz, 1 H), 4.12-4.25 (m, 4 H), 5.17 (brs, 1 H); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 15.17, 16.34 (d, JCP ) 6.1 Hz), 16.50 (d, JCP ) 6.1 Hz), 27.11, 28.29, 31.06 (d, JCP ) 219 Hz), 60.85, 62.55 (d, JCP ) 6.9 Hz), 63.12 (d, JCP ) 6.1 Hz), 81.10, 157.1; IR (neat) 3420, 3280, 2984, 2936, 1720, 1696, 1251 cm-1; MS (EI) m/z 323; exact mass M+ 323.1492 (calcd for C13H26O6NP 323.1497). r-1-Amino-t-2-(hydroxymethyl)-1-cyclopropanephosphonic Acid (13). HCl ether solution, 1 N (14.6 mL, 14.6 mmol), was added to 12 (118 mg, 0.365 mmol) at 0 °C. The reaction mixture was allowed to warm to room temperature,

Yamazaki et al. stirred for 18 h, and then concentrated in vacuo. The residue was dissolved in water (1.5 mL) and basified with NaHCO3 (ca. 300 mg). The mixture was extracted with CH2Cl2 (×10) and the combined organic layer was dried (Na2SO4) and concetrated in vacuo to give crude diethyl 2-hydroxymethyl1-amino-1-cyclopropanephosphonate (66 mg, ca. 80%). To a stirred solution of this aminocyclopropane (66 mg, 0.29 mmol) in CH2Cl2 (1.3 mL) at room temperature was added iodotrimethylsilane (0.170 mL, 113 mg, 2.08 mmol). The reaction mixture was stirred for 1 h and then concentrated in vacuo. The residue was dissolved in absolute ethanol (1.4 mL) and treated with propylene oxide (135 µL, 113 mg, 2.08 mmol). After standing overnight at room temperature, the precipitates were separated and washed with ethanol to give 13 (39 mg, 64% from 12) as a hygroscopic solid. 13: mp 71-73 °C; 1H NMR (400 MHz, D2O) δ (ppm) 0.94-1.04 (m, 1 H), 1.16-1.24 (m, 1 H), 1.52-1.60 (m, 1 H), 3.67 (dd, J ) 12.3, 6.4 Hz, 1 H), 3.87 (dd, J ) 12.3, 4.6 Hz, 1 H); 13C NMR (100.6 MHz, D2O) δ (ppm) 12.74 (CH2, JCH ) 165 Hz), 21.82 (CH, JCH ) 164 Hz), 34.55 (C, JCP ) 199 Hz), 58.90 (CH, JCH )145 Hz); IR (KBr) 3400-2600, 1609, 1240 cm-1; MS (FAB) m/z 168 (MH+).

Acknowledgment. We are grateful to Dr. K. Yamamoto (Osaka University) for measurement of mass and NMR spectral data (500 and 600 MHz). Supporting Information Available: 1H and 13C NMR spectra for compounds 3d-e and 7-13 and 2D-NOESY spectra for compounds 3a, 3c, and 3f (30 pages). This material is contained in libraries on microfiche, immediately follows this article in the microfilm version of the journal, and can be ordered from the ACS; see any current masthead page for ordering information. JO9805450